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Activated microglia-induced inflammation in the hippocampus plays an important role in perioperative neurocognitive disorders. Previous studies have shown that sialic acid-binding immunoglobulin-like lectin 3 (hSiglec-3, ortholog of mouse Siglec-E) engagement in microglia and its glycan ligands on neurons contributes to inflammatory homeostasis through an endogenous negative regulation pathway. This study aimed to explore whether the glycan ligand alteration on neurons plays a role in sevoflurane-induced perioperative neurocognitive disorders. This study's data has shown that a slight Siglec-E ligands' expression decrease does not induce inflammation homeostasis disruption. We also demonstrated that the ligand level on neurons was decreased with age, and the reduced Siglec-E ligand expression on neurons caused via sevoflurane was induced by neuraminidase 1. Furthermore, this study has shown that the Siglec-E ligand expression decline caused by age and sevoflurane treatment could decrease the ligands' level, thus leading to inflammatory homeostasis disruption. This research provided a novel mechanism for perioperative neurocognitive disorder susceptibility in the elderly., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The immature immune system at birth and environmental stress increase the risk of infection in nursing pigs. Severe infection subsequently induces intestinal and respiratory diseases and even cause death of pigs. The nutritional and physiological conditions of sows directly affect the growth, development and disease resistance of the fetus and newborn. Many studies have shown that providing sows with nutrients such as functional oligosaccharides, oils, antioxidants, and trace elements could regulate immunity and the inflammatory response of piglets. Here, we reviewed the positive effects of certain nutrients on milk quality, immunoglobulin inflammatory response, oxidative stress, and intestinal microflora of sows, and further discuss the effects of these nutrients on immunity and the inflammatory response in the offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yang, Zhang, Liu, Wu, Qi, Guan, Ren and Zhang.)

The placenta controls the growth of the fetus and ensures its immune protection. Key to these functions, the syncytiotrophoblast (SYN) is a syncytium formed by fusion of underlying mononuclear trophoblasts. The SYN covers the placental surface and is bathed in maternal blood to mediate nutritional and waste exchanges between the mother and fetus. The bacterial pathogen Listeria monocytogenes breaches the trophoblast barrier and infects the placental/fetal unit resulting in poor pregnancy outcomes. In this work, we analyzed the L. monocytogenes intracellular lifecycle in primary human trophoblasts. In accordance with previous studies, we found that the SYN is 20-fold more resistant to infection compared to mononuclear trophoblasts, forming a protective barrier to infection at the maternal interface. We show for the first time that this is due to a significant reduction in L. monocytogenes uptake by the SYN rather than inhibition of the bacterial intracellular division or motility. We here report the first transcriptomic analysis of L. monocytogenes -infected trophoblasts (RNA sequencing). Pathway analysis showed that infection upregulated TLR2, NOD-like, and cytosolic DNA sensing pathways, as well as downstream pro-inflammatory circuitry (NF-κB, AP-1, IRF4, IRF7) leading to the production of mediators known to elicit the recruitment and activation of maternal leukocytes (IL8, IL6, TNFα, MIP-1). Signature genes associated with poor pregnancy outcomes were also upregulated upon infection. Measuring the release of 54 inflammatory mediators confirmed the transcriptomic data and revealed sustained production of tolerogenic factors (IL-27, IL-10, IL-1RA, TSLP) despite infection. Both the SYN and mononuclear trophoblasts produced cytokines, but surprisingly, some cytokines were predominantly produced by the SYN (IL-8, IL-6) or by non-fused trophoblasts (TNFα). Collectively, our data support that trophoblasts act as placental gatekeepers that limit and detect L. monocytogenes infection resulting in a pro-inflammatory response, which may contribute to the poor pregnancy outcomes if the pathogen persists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Johnson, Azari, Webb, Zhang, Gavrilin, Marshall, Rood and Seveau.)

Systemic low-grade inflammation and imbalance of gut microbiota are important risk factors promoting the progression of obesity-related metabolic disorders. This provides potential pharmacological and nutritional targets for the management of obesity and obesity-related disorders. Here, we evaluated the modulatory effects of nanosilver on obesity-related systemic low-grade inflammation and gut microbial dysbiosis. C57BL/6J mice were fed with normal diet (ND) or high-fat diet (HFD) for 6 months, with/without nanosilver supplementation in drinking water. Nanosilver administration showed little systemic toxicity and did not affect the progression of obesity but mitigated the obesity-related systemic low-grade inflammation in obese mice. Such mitigation of systemic low-grade inflammation was specifically mediated by reducing the inflammatory status of epididymal visceral white adipose tissue (eWAT). Nanosilver treatments increased the diversity of gut microbial communities and markedly recovered the relative abundance of Verrucomicrobia, Epsilonbacteraeota, Actinobacteria, and Deferribacteres, without altering the proportion of Bacteroidetes or Firmicutes. The beneficial effects of nanosilver in obese mice were in association with an increase in Akkermansia but a decrease in Parasutterella at the genus level. This study suggested a potential application of nanosilver in reducing the health risks of obesity.

Toxoplasma gondii is a protozoan parasite that can cause a latent infection in the central nervous system, leading to neurobehavioral abnormalities in the host. However, the mechanism underlying these changes remains relatively unexplored. In this study, we detected behavioral changes, pathological injury, secretion of neurotransmitters and related signal pathway in mice infected by T. gondii using behavioral test, histopathology, immunofluorescence staining, western blotting, HPLC and real time PCR. Mice showed neurobehavioral disturbances two months after infection with T. gondii. Histopathology revealed the activation of astrocytes and microglia, apoptosis of neurons and decreases in synapses in the brain of infected mice. Excessive secretion of cytokines and chemokines was detected in the brains of mice infected by T. gondii compared to uninfected mice. Furthermore, T. gondii infection led to abnormalities in neurotransmitters and the activation of NF-κB and dopamine (DA) signaling pathways in the infected mice. In conclusion, excessive activation of the inflammation in the brain could induce neuronal apoptosis in mice chronically infected with T. gondii. Dysregulation of the dopaminergic neurotransmitter could provide an explanation of neurobehavioral disorders in infected hosts., (Copyright © 2018. Published by Elsevier B.V.)

Arthus reaction (AR), a type of unconventional immune complex-mediated inflammation, is likely accompanied by alterations in circulating metabolites. Here, a proton nuclear magnetic resonance ((1)H NMR) spectroscopy method coupled with a rapid resolution liquid chromatography (RRLC) method was developed to evaluate the systemic metabolic consequences of AR and characterize metabolic aberrations. Serum and urine samples from AR rats and normal controls were compared to determine whether there were significant alterations associated with AR. The partial least squares discriminant analysis (PLS-DA) models of metabolomic results demonstrated good intergroup separations between AR rats and normal controls. Multivariate statistical analysis revealed significant alterations in the levels of 34 metabolites, which were termed as the disease-associated biomarkers. Differential metabolites identified from the metabolomic analysis suggested that AR caused dysfunctions of kidney and liver accompanied with changes in widespread metabolic pathways including the tricarboxylic acid (TCA) cycle, gut microbiota metabolism, lipids and cell membranes metabolism, glucose metabolism, fatty acid β-oxidation, amino acids metabolism and ketogenesis. This study assessed and provided important metabolomic variations in serum and urine associated with AR and, therefore, demonstrated metabolomics as a powerful approach for the complete elucidation of the underlying pathophysiologic mechanisms of AR.

Objective: This study investigates the relationship between post-heparin plasma lipoprotein lipase (LPL) activity, chronic inflammation and premature stable coronary artery disease (CAD) in male patients., Methods and Results: 132 male patients (< 55 years) with documented stable CAD (cases) and 130 male subjects without CAD were enrolled. Cases had higher values of high-sensitivity C-reactive protein (hs-CRP) and lower LPL activity [(5.31 +/- 3.06) mg/l vs. (2.67 +/- 1.01) mg/l, P < 0.01; (27.39 +/- 6.71) nmol x ml(-1) x min(-1) vs. (37.06 +/- 7.22) nmol x ml(-1) x min(-1), P < 0.01, respectively]. LPL activity was inversely associated with hs-CRP and triglycerides (TG), and positively associated with HDL-C (r = -0.761, P < 0.001; r = -0.339, P < 0.001; r = 0.217, P < 0.05; respectively) in cases. In multivariate analysis, higher values of hs-CRP (OR 1.45, 95% CI: 1.083-1.951; P = 0.013), BMI, LDL-C and hypertension were significant predictors of premature stable CAD in male patients. Higher LPL activity decreases risk of premature stable CAD (OR 0.87, 95% CI: 0.809-0.933; P = 0.000). LPL activities decreased with the increased number of significantly stenosed vessels (P < 0.05)., Conclusions: LPL activity and hs-CRP are significant predictors of premature stable CAD in male patients and are inversely correlated.

Background Activation of nuclear factor-kappa B (NF-κB) signalling is key in the pathogenesis of chronic kidney disease (CKD). However, a certain level of NF-κB activity is necessary to enable tissue repair. Methods The relationship between activated and inactivated NF-κB signaling and the pathogenesis of CKD was investigated using mouse models of NF-κB partial inactivation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into alanine) and activation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into serine). Results The density of CD3, CD8, CD68 positive cells, as well as the expression of interleukin 6, Tumor necrosis factor receptor associated factor 1 and Nef-associated factor 1 in the kidney tissues of NF-κBC59A mice were reduced, whereas an opposing pattern was observed in the NF-κBC59S mice. Blood pressure, kidney fibrosis (analyzed by periodic acid–Schiff, Masson trichrome and Sirius Red staining, as well as α-SMA immunofluorescence), serum creatinine and urinary albumin-to-creatinine ratio are markedly increased in NF-κB-activated and -inactivated mice compared with controls. Transmission electron microscopy indicated that the glomerular basement membrane was thicker in both NF-κBC59A and NF-κBC59S mice compared with wild-type mice. Conclusions Using mice models with partially activated and inactivated NF-κB pathways suggests that there is an apparently U-shaped relationship between blood pressure, kidney function as well as morphology and the activation of the NF-κB pathway. A certain optimal activity of the NF-κB pathway seems to be important to maintain optimal kidney function and morphology. [ABSTRACT FROM AUTHOR]

Background: Previous studies have initially reported accompanying elevated 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function. Methods: Twelve AMI rats and six Sham rats serially underwent [68Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. Results: The uptake of [68Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). Conclusions: Corresponding with the peaked [68Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is the sixth leading cause of death in the USA. It is established that neuroinflammation contributes to the synaptic loss, neuronal death, and symptomatic decline of AD patients. Accumulating evidence suggests a critical role for microglia, innate immune phagocytes of the brain. For instance, microglia release pro-inflammatory products such as IL-1β which is highly implicated in AD pathobiology. The mechanisms underlying the transition of microglia to proinflammatory promoters of AD remain largely unknown. To address this gap, we performed reduced representation bisulfite sequencing (RRBS) to profile global DNA methylation changes in human AD brains compared to no disease controls. We identified differential DNA methylation of CASPASE-4 (CASP4), which when expressed promotes the generation of IL-1β and is predominantly expressed in immune cells. DNA upstream of the CASP4 transcription start site was hypomethylated in human AD brains, which was correlated with increased expression of CASP4. Furthermore, microglia from a mouse model of AD (5xFAD) express increased levels of CASP4 compared to wild-type (WT) mice. To study the role of CASP4 in AD, we developed a novel mouse model of AD lacking the mouse ortholog of CASP4 and CASP11, which is encoded by mouse Caspase-4 (5xFAD/Casp4−/−). The expression of CASP11 was associated with increased accumulation of pathologic protein aggregate amyloid-β (Aβ) and increased microglial production of IL-1β in 5xFAD mice. Utilizing RNA-sequencing, we determined that CASP11 promotes unique transcriptomic phenotypes in 5xFAD mouse brains, including alterations of neuroinflammatory and chemokine signaling pathways. Notably, in vitro, CASP11 promoted generation of IL-1β from macrophages in response to cytosolic Aβ through cleavage of downstream effector Gasdermin D (GSDMD). Therefore, here we unravel the role for CASP11 and GSDMD in the generation of IL-1β in response to Aβ and the progression of pathologic inflammation in AD. Overall, our results demonstrate that overexpression of CASP4 due to differential DNA methylation in AD microglia contributes to the progression of AD pathobiology. Thus, we identify CASP4 as a potential target for immunotherapies for the treatment and prevention of AD. [ABSTRACT FROM AUTHOR]

Nucleotide-binding and oligomerization domain-like receptors (NOD-like receptors, NLRs) can regulate the inflammatory response to eliminate pathogens and maintain the host's homeostasis. In this study, the head kidney macrophages of Siberian sturgeon were treated with lipopolysaccharide (LPS) to induce inflammation by evaluating the expression of cytokines. The high-throughput sequencing for macrophages after 12 h treatment showed that 1224 differentially expressed genes (DEGs), including 779 upregulated and 445 downregulated, were identified. DEGs mainly focus on pattern recognition receptors (PRRs) and the adaptor proteins, cytokines, and cell adhesion molecules. In the NOD-like receptor signaling pathway, multiple NOD-like receptor family CARD domains containing 3-like (NLRC3-like) were significantly downregulated, and pro-inflammatory cytokines were upregulated. Based on the transcriptome database, 19 NLRs with NACHT structural domains were mined and named in Siberian sturgeon, including 5 NLR-A, 12 NLR-C, and 2 other NLRs. The NLR-C subfamily had the characteristics of expansion of the teleost NLRC3 family and lacked the B30.2 domain compared with other fish. This study revealed the inflammatory response mechanism and NLRs family characterization in Siberian sturgeon by transcriptome and provided basic data for further research on inflammation in teleost. [ABSTRACT FROM AUTHOR]

Background: 18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD). Methods: Patients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries. Results: 100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P <.001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P <.001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P <.001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors. Conclusions: Coronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD. [ABSTRACT FROM AUTHOR]

(1) This study compared [68Ga]PentixaFor uptake in active arterial segments with corresponding [18F]FDG arterial uptake as well as the relationship with cardiac [68Ga]PentixaFor uptake. (2) Method: Tracer uptake on atherosclerotic lesions in the large arteries was measured and target-to-background ratios (TBR) were calculated to adjust background signals with two investigators blinded to the other PET scan. On a patient-based and lesion-to-lesion analysis, TBR values of two tracers were compared and the relationship with cardiac inflammation was further explored. Furthermore, two cardiovascular risk-related groups were divided to explore the value of risk stratification of the two tracers in atherosclerosis. (3) Results: [68Ga]PentixaFor PET/MRI identified more lesions (88% vs. 48%; p < 0.001) and showed higher uptake than [18F]FDG PET/MRI (TBR, 1.90 ± 0.36 vs. 1.63 ± 0.29; p < 0.001). In the patient-based analysis, the TBR of [68Ga]PentixaFor uptake was also significantly higher than [18F]FDG uptake (1.85 ± 0.20 vs. 1.42 ± 0.19; p < 0.001). The TBR of active lesions for [68Ga]PentixaFor was significantly increased in the high-risk group (n = 9), as compared to the low-risk group (n = 10) (2.02 ± 0.15 vs. 1.86 ± 0.10, p = 0.015), but not for [18F]FDG (1.85 ± 0.10 vs. 1.80 ± 0.07, p = 0.149). (4) Conclusion: [68Ga]PentixaFor PET/MRI identified many more lesions than [18F]FDG PET/MRI. Patients with high-risk cardiovascular factors illustrated an increased uptake of [68Ga]PentixaFor. There was a correlation between the elevated uptake of [68Ga]PentixaFor in the active arterial segments and heart. [ABSTRACT FROM AUTHOR]

Excessive monocyte activation with the development of excessive or uncontrolled release of proinflammatory cytokines often results in host tissue injury and even death in patients with pneumonia caused by the 2019 novel coronavirus. However, the changes of cytokine profiles of coronavirus disease 2019 (COVID‐19) patients, as well as the underlying mechanisms that are involved, remain unknown. Using a cytokine array containing 174 inflammation‐related cytokines, we found significantly altered cytokine profiles in severe COVID‐19 patients compared with those in mild patients or healthy controls, and identified leptin, CXCL‐10, IL‐6, IL‐10, IL‐12, and TNF‐α as the top differentially expressed cytokines. Notably, leptin showed high consistency with CXCL‐10 and TNF‐α in predicting disease severity, and correlated with body mass index, decreased lymphocyte counts, and disease progression. Further analysis demonstrated that monocytes in severe patients with higher leptin levels were inclined toward M1 polarization. Mechanistic studies revealed that leptin synergistically up‐regulated expression levels of inflammatory cytokines and surface markers with IL‐6 in monocytes through STAT3 and NF‐κB signaling pathways. Collectively, our results suggest that overweight COVID‐19 patients were prone to have higher leptin levels, which further activated monocytes, resulting in amplified or dysregulated immune responses. Taken together, our findings argue that leptin correlates severity of COVID‐19 and may indicate a possible mechanism by which overweight patients have a greater tendency to develop severe conditions. [ABSTRACT FROM AUTHOR]

Background: Post-ischemic inflammatory response might be affected by many factors. We chose leukocyte count as a marker of inflammatory response and investigated whether the effects of leukocyte count on the clinical outcomes in acute ischemic stroke patients are different according to different factors. Methods: We derived data from the China National Stroke Registry II. Patients with ischemic stroke were classified into four groups by leukocyte count quartiles within the first 24 h after admission. Adverse clinical outcomes were defined as recurrent stroke, all-cause death, and poor functional outcomes (3 ≤ mRS ≤ 5) at 3-months and 1-year follow-up. The subgroup factors were age, sex, history of hypertension, history of diabetes, history of previous stroke, or transient ischemic attack and smoking status. We assessed the association between leukocyte count and adverse clinical outcomes and evaluated this association in different subgroups. Results: A total of 14,678 patients were included. Patients in higher quartiles were likely to be younger, male, smokers, and drinkers, and to have a shorter time from symptom onset to arrival, a more proportion of history of diabetes, atrial fibrillation, and hypertension, and a higher severity of stroke. Higher quartiles were associated with elevated risk of adverse clinical outcomes at 3-months and 1-year follow-up. Leukocyte count had a moderate accuracy to predict clinical outcomes. There was no difference in the relationship between leukocyte count and adverse clinical outcomes across subgroups such as age, sex, history of hypertension, and smoking. The effect of leukocyte count on all-cause death was pronounced among patients with previous stroke or transient ischemic attack, and the effect of leukocyte count on short-term poor functional outcomes was also pronounced among patients without diabetes. Conclusions: Leukocyte count is associated with short-term and long-term clinical outcomes of acute ischemic stroke and may have predictive value, especially in patients with certain specific characteristics. [ABSTRACT FROM AUTHOR]

Highlights • A novel image segmentation method for quantification of myelinated fibers in brain sections. • The developed algorithm converted to a program called" MyelinQ". • The program is automated, consistent and easy-to-use. • The method revealed that a viral mimic causes significant hypomyelination in neonatal mouse brain. Abstract The developing brain is very susceptible to environmental insults, and very immature infants often suffer from long-term neurological syndromes associated with white matter injuries such as periventricular leukomalacia. Infection and inflammation are important risk factors for neonatal brain white matter injuries, but the evaluation of white matter injury in animal models, especially the quantification of myelinated axons, has long been problematic due to the lack of ideal measurement methods. Here, we present an automated segmentation method, which we call MyelinQ, for the quantification of myelinated white matter in immunohistochemical DAB-stained sections of the neonatal mouse brain. Using MyelinQ, we show that a viral infection mimic agent, the Toll-like receptor 3 ligand Poly I:C, causes significant hypomyelination of white matter in the cortical and hippocampal fimbria regions, but not in the striatal caudoputamen region. We showed that MyelinQ can reliably produce results that are comparable to a method used in our previous publications. However, in comparison to the conventional method, MyelinQ has the advantages of being automated, objective and accurate. MyelinQ can analyze white matter in various specific brain regions and therefore provides a useful platform for the quantification of myelin and the evaluation of white matter injuries in animal models. MyelinQ and its code together with instructions for use can be found at: https://github.com/parham-ap/myelinq. [ABSTRACT FROM AUTHOR]

Background: Interleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention. Objective: The purpose of this study was to investigate whether IL-10 gene polymorphisms and plasma protein expression are associated with CP and to analyze the role of IL-10 in CP. Methods: A total of 282 CP patients and 197 healthy controls were genotyped for IL-10 polymorphisms (rs1554286, rs1518111, rs3024490, rs1800871, and rs1800896). Among them, 95 CP patients and 93 healthy controls were selected for plasma IL-10 measurement. results: The differences in the rs3024490 (p = 0.033) and rs1800871 (p = 0.033) allele frequencies of IL-10 were determined between CP patients and controls. The frequencies of allele and genotype between CP patients with spastic tetraplegia and normal controls of IL-10 polymorphisms showed significant differences for rs1554286, rs151811, rs3024490, rs1800871, and rs1800896 (pallele = 0.015, 0.009, 0.006, 0.003, and 0.006, pgenotype = 0.039, 0.018, 0.027, 0.012, and 0.03, respectively). The plasma IL-10 protein level in CP patients was higher than normal controls (9.13 ± 0.77 vs. 6.73 ± 0.63 pg/ml, p = 0.017). IL-10 polymorphisms and protein association analysis showed that the TT genotype had higher plasma IL-10 protein levels compared to the GG + GT genotype at rs3024490 (11.14 ± 7.27 vs. 7.44 ± 6.95 pg/ml, p = 0.045, respectively) in CP cases. conclusion: These findings provide an important contribution toward explaining the pleiotropic role of IL-10 in the complex etiology of CP. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of iced tea lotion in oral care of middle-aged and elderly patients with diabetes mellitus. Methods A total of 90 middle-aged and elderly patients with diabetes mellitus were recruited. They were randomly divided to control group (n=45) and observation group (n=45), and treated by oral care of normal saline and ice tea lotion, respectively. Oral malodor, swelling and congestion of oral mucosa and culture results of oral throat swab between groups were compared. Results The incidence of oral malodor, swelling and congestion of oral mucosa was significantly lower in observation group than that of control group(P＜0. 05). The positive rates of fungi was 8. 89%(4/45) in the observation group, which was lower than 60. 00%(27/45) in the control group (P＜0. 05). Conclusion Oral care with iced tea lotion is potentially effective to decrease the incidence of oral diseases in middle-aged and elderly patients with diabetes mellitus. (目的 探讨冰茶洗剂在中老年糖尿病患者口腔护理中的临床效果。方法 90例中老年糖尿病患者随机分为对照组与观察组, 各45例。对照组采用生理盐水进行口腔护理, 观察组采用冰茶洗剂进行口腔护理。对比2组患者的口腔异味、口腔黏膜红肿充血情况、口腔咽拭子培养情况。结果 观察组口腔异味以及口腔黏膜红肿充血发生率均低于对照组, 差异有统计学意义(P＜0. 05)。观察组咽拭子白色附着物真菌培养阳性率8. 89%(4/45), 低于对照组的60. 00%(27/45), 差异有统计学意义(P＜0. 05)。结论 冰茶洗剂可以有效改善中老年糖尿病患者的口腔问题, 减少口腔疾患的发生。)

Purpose: PET with F-FDG has the potential to assess vascular macrophage metabolism. F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. Methods: The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUV) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated. Results: Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUV values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBR values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUV and TBR values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBR values may also be expected with PET/MRI compared with PET/CT. Conclusion: SUV and TBR values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUV and TBR with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI. [ABSTRACT FROM AUTHOR]

Abstract: (−)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic compound present in green tea and has been shown to possess anti-inflammatory and anti-oxidative properties. In this study, we investigated the protective effects of EGCG against concanavalin A (ConA)-induced liver injury and the underlying mechanisms. EGCG (5mg/kg) was administered orally by gavage to mice twice daily for 10 days before an intravenous injection of ConA. We found that EGCG effectively rescued lethality, improved hepatic pathological damage, and decreased serum levels of alanine aminotransaminase (ALT) in ConA-challenged mice. Furthermore, EGCG also significantly prevented the release of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-6 in serum, reduced malondialdehyde (MDA) levels, and restored glutathione (GSH) content and superoxide dismutase (SOD) activity in liver tissues from ConA-challenged mice. Finally, nuclear factor (NF)-κB activation and expression levels of Toll-like receptor (TLR) 2, TLR4 and TLR9 protein in liver tissues were significantly inhibited by EGCG pretreatment. Taken together, our data suggest that EGCG possesses hepatoprotective properties against ConA-induced liver injury through its anti-inflammatory and anti-oxidant actions. [Copyright &y& Elsevier]

A translocator protein 18 kDa targeted radiotracer, N,N-diethyl-2-(2-(4-[18F]fluorophenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl) acetamide ([18F]FDPA), was automated synthetized and evaluated for cardiac inflammation imaging. Various reaction conditions for an automated synthesis were systematically optimized. MicroPET/CT imaging were performed on normal rats and rats with myocardial infarction (MI). Normalized SUV ratios of [18F]FDPA to [13N]NH3 (NSRs) in different regions were calculated to normalize the uptake of [18F]FDPA to perfusion. The amount of TBAOMs and the volume/proportion of water were crucial for synthesis. After optimization, the total synthesis time was 68 min. The non-decay corrected radiochemical yields (RCYs) and molar activities were 19.9 ± 1.7% and 169.7 ± 46.5 GBq/μmol, respectively. In normal rats, [18F]FDPA showed a high and stable cardiac uptake and fast clearance from other organs. In MI rats, NSRs in the peri-infarct and infarct regions, which were infiltrated with massive inflammatory cells revealed by pathology, were higher than that in the remote region (1.20 ± 0.01 and 1.08 ± 0.10 vs. 0.89 ± 0.05, respectively). [18F]FDPA was automated synthesized with high RCYs and molar activities. It showed a high uptake in inflammation regions and offered a wide time window for cardiac imaging, indicating it could be a potential cardiac inflammation imaging agent. [ABSTRACT FROM AUTHOR]

Background: The toxicity of released metallic particles generated in metal-on-metal (MoM) total hip arthroplasty (THA) using cobalt chromium (CoCr) has raised concerns regarding their safety amongst both surgeons and the public. Soft tissue changes such as pseudotumours and metallosis have been widely observed following the use of these implants, which release metallic by-products due to both wear and corrosion. Although activated fibroblasts, the dominant cell type in soft tissues, have been linked to many diseases, the role of synovial fibroblasts in the adverse reactions caused by CoCr implants remains unknown. To investigate the influence of implants manufactured from CoCr, the periprosthetic synovial tissues and synovial fibroblasts from patients with failed MoM THA, undergoing a revision operation, were analysed and compared with samples from patients undergoing a primary hip replacement, in order to elucidate histological and cellular changes. Results: Periprosthetic tissue from patients with MoM implants was characterized by marked fibrotic changes, notably an increase in collagen content from less than 20% to 45–55%, an increase in α-smooth muscle actin positive cells from 4 to 9% as well as immune cells infiltration. Primary cell culture results demonstrated that MoM synovial fibroblasts have a decreased apoptosis rate from 14 to 6% compared to control synovial fibroblasts. In addition, synovial fibroblasts from MoM patients retained higher contractility and increased responsiveness to chemotaxis in matrix contraction. Their mechanical properties at a single cell level increased as observed by a 60% increase in contraction force and higher cell stiffness (3.3 kPa in MoM vs 2.18 kPa in control), as measured by traction force microscopy and atomic force microscopy. Further, fibroblasts from MoM patients promoted immune cell invasion by secreting monocyte chemoattractant protein 1 (MCP-1, CCL2) and induced monocyte differentiation, which could also be associated with excess accumulation of synovial macrophages. Conclusion: Synovial fibroblasts exposed in vivo to MoM THA implants that release CoCr wear debris displayed dramatic phenotypic alteration and functional changes. These findings unravelled an unexpected effect of the CoCr alloy and demonstrated an important role of synovial fibroblasts in the undesired tissue reactions caused by MoM THAs. [ABSTRACT FROM AUTHOR]

• A large SUA variation was associated with a higher risk of CVD and its subtypes. • Both a large rise or fall in SUA was associated with a higher risk of CVD. • The harmful effect of a large variation of SUA on CVD was more pronounced in older adults than that in young adults. • The hazardous effect of SUA variation on CVD was mainly induced by excessive inflammation and elevated blood pressure. The association of serum uric acid (SUA) with cardiovascular disease (CVD) is inconsistent and limited by a single measurement of SUA. This study aimed to investigate the association of SUA variation, considering its magnitude and direction, with the risk of CVD. This study included 41,578 participants with four biennial measurements of SUA during 2006–2012 from the Kailuan study. SUA variation was measured using the coefficient of variation (primary index), standard deviation, average real variability, and variability independent of mean, and the direction of variation was also assessed. Multivariate-adjusted Cox regressions were used to assess the associations, and Bayesian network was utilized to find the most important pathway from SUA variation to CVD. During a median follow-up of 6.74 (interquartile range: 6.45–7.03) years, we identified 1,852 (4.45%) cases of incident CVD. A large SUA variation (top vs. bottom tertiles) was associated with a higher risk of CVD (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.11–1.40), especially in older adults than that in young adults (P int =0.0137). The higher risk of CVD was observed with both large rises (HR, 1.24; 95% CI, 1.10–1.39) and falls (HR, 1.19; 95% CI, 1.03–1.38) in SUA variation. The hazardous effect of SUA variation on CVD was mainly induced by excessive inflammation and elevated blood pressure. Similar results were observed for CVD subtypes. Elevated SUA variation was associated with a higher risk of CVD, irrespective of the direction of SUA variation, and inflammation played an important role in the pathway. [ABSTRACT FROM AUTHOR]

Background: The inflammatory response of vascular endothelial cells plays important roles in the initiation and progression of atherosclerotic lesions. EphA2 receptor activation promotes the endothelial cell inflammatory response, and its expression is increased in the endothelial cell layer of atherosclerotic plaques. However, the association between EphA2 and atherosclerosis has not been determined. Methods: Eight-week-old male ApoE−/− mice were systemically infected with adenoassociated virus serotype 9 carrying a small hairpin RNA specifically targeting the EphA2 gene to knock down EphA2 expression in aortic endothelial cells. These mice were then fed a high-cholesterol diet for 12 weeks. Blood was collected for the measurement of plasma lipids. The aortas were harvested to evaluate the atherosclerotic lesion size, macrophage components, and expression of proinflammatory genes using Oil Red O staining, immunofluorescence staining, and molecular biology analysis. Results: The lesions formed in the entire aorta and aortic sinus of the ApoE−/− mice with EphA2 knockdown were significantly smaller than those in the control mice (10.7%±3.1% versus 25.1%±4.2%; 0.51±0.02mm2 versus 0.85±0.03mm2; n =10; P <.05). Furthermore, the lesions in the ApoE−/− mice with EphA2 knockdown displayed reduced inflammation compared with the control mice, as reflected by the decreased macrophage infiltration (8.2%±2.9% versus 22.7%±4%; n =10; P <.05); decreased nuclear factor-κβ activation; and diminished expression of vascular cell adhesion molecule-1, E-selectin, and monocyte chemotactic protein-1 (all P <.05). Conclusions: Our data demonstrate that the EphA2 receptor silencing attenuates the extent and inflammation of atherosclerotic lesions in ApoE−/− mice. Thus, EphA2 knockdown in endothelial cells represents a novel therapeutic strategy for patients with atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective. To explore the diagnosis value of inflammatory markers and cytokines in neonatal sepsis. Methods. In this retrospective analysis, 90 cases of neonatal sepsis admitted to our hospital from April 2019 to April 2021 were included in the observation group, and 70 healthy neonates who received routine physical examinations in our hospital during the same period were recruited as the control group. Comparison and analysis of inflammatory markers and cytokines levels between the two groups were performed on days 1, 3, and 7 after the onset. Flow cytometry was used to measure the white blood cells (WBCs) and percentage of neutrophils (N%), immunoturbidimetry was used to determine C-reactive protein (CRP), immunochromatographic analysis was used to determine procalcitonin (PCT) in plasma, and the enzyme-linked immunosorbent assay was used to determine interleukin-27 (IL-27), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). Results. Compared with healthy controls, neonatal sepsis resulted in significantly higher levels of WBC, N%, PCT, and CRP on days 1, 3, and 7 after onset. The levels of WBC, N%, and PCT were continuously decreased from day 1 to day 7, while the levels of CRP were increased on day 1 and day 3 but declined on day 7 (P < 0.05). Compared with healthy controls, patients with sepsis showed higher levels of IL-27, IL-6, IL-10, and TNF-α on days 1, 3, and 7 after the onset. The levels of IL-27, IL-6, and IL-10 were increased on day 1 and day 3 but decreased on day 7, and the levels of TNF-α were continuously decreased from day 1 to day 7 (all P < 0.05). Conclusion. Neonatal sepsis was associated with fluctuating levels of WBC, N%, PCT, CRP, IL-27, IL-6, IL-10, and TNF-α at different time points of disease. The joint detection of the above indices provides a new pathway for the early diagnosis of neonatal sepsis. [ABSTRACT FROM AUTHOR]

Tea (Camellia sinensis) has been consumed for centuries as a traditional remedy for various metabolic diseases. The pharmacological mechanisms of many conventional medicines, including tea, often need to be clarified. Chin brick tea is a unique Chinese black tea grown in Hubei, China, rich in tea elements such as tea polyphenols and tea polysaccharides. We focus on the effects of commercial chin brick tea on non-alcoholic fatty liver disease by altering intestinal flora and its metabolite, bile acids. Targeted UPLC-MS/MS was employed to quantify the tea elements in commercial chin brick tea. In this study, we performed an integrated approach of animal experiments, 16 S rDNA, and ultra-performance liquid chromatography-tandem mass spectrometry to explore the potential mechanism of action of chin brick tea in preventing non-alcoholic fatty liver disease (NAFLD). After 14 weeks of administration, CBT extract could signiffcantly decrease the levels of body weight, liver weight, LDL-C, TC, ALT, IL-1β and IL-18, and slight increase HDL-C levels in NAFLD mice. The results indicated that the interventional impact of CBT with high-fat diet-induced NAFLD might depend on intestinal flora and its metabolites bile acids. Moreover, sequencing of 16 S rRNA genes demonstrated that CBT could signiffcantly improve the intestinal flora disorder of NAFLD mice. Speciffcally, CBT increased the levels of Lactobacillus, Alloprevotella, and Ruminococcaceae, while reducing the levels of Bacteroides in NAFLD mice. Then, a total of 23 bile acids were identified, 17 differential bile acids were obtained by screening, and CBT increase the primary bile acids/secondary bile acids ratio in NAFLD mice. Additionally, correlation analysis revealed that Bacteroides was negatively correlated with DCA and ωMCA, Lactobacillus was positively correlated with DCA and ωMCA, Bacteroides was positively correlated with NAFLD, Lactobacillus was negatively associated with NAFLD, and DCA and ωMCA were negatively correlated with NAFLD. CBT extract has a good interventional impact on NAFLD mice. The mechanism by which this extract exerts its action is, at least partly, related to its regulation of intestinal flora and its metabolites bile acids. [Display omitted] [ABSTRACT FROM AUTHOR]

Accompanied by overproduction of oxidants and reduction of pH, inflammation is closely related to many diseases such as cancer, atherosclerosis, and asthma. Besides chemotherapeutic agents, the potential regulative role of autophagy in inflammation is being actively investigated. RNA interference (RNAi)-based gene therapy is widely explored for clinical therapy but seriously restricted by lack of suitable carriers. In this study, we synthesized a hyaluronan-based ROS-sensitive polymer which was expected to release loaded chemical drugs in inflammatory environment and further developed a stable and nontoxic co-delivery nanosystem of siRNA targeting autophagy suppressive gene and chemotherapeutic agents. The in vitro transfection study of this nanosystem revealed improved intracellular accumulation of siRNA and excellent gene silencing efficacy comparable to that of conventional cationic liposome. Moreover, the mRNA expression of inflammatory cytokines was remarkably decreased by our nanosystem. Considering its biocompatibility, transfection efficacy, and anti-inflammatory capability, this co-delivery nanosystem proclaimed to be a promising combined therapeutic strategy for enhanced anti-inflammatory therapy. [ABSTRACT FROM AUTHOR]

Purpose: This study compared the effect of immediate versus delayed massage-like compressive loading (MLL) on peak isometric torque recovery and inflammatory cell infiltration after eccentric exercise (EEX). Methods: Eighteen skeletally mature New Zealand White rabbits were instrumented with peroneal nerve cuffs for the stimulation of hindlimb tibialis anterior muscles. After a bout of EEX, rabbits were randomly assigned to an MLL protocol (0.5 Hz, 10 N, 15 min) that started immediately post-EEX, 48 h post-EXX, or no-MLL control and performed for four consecutive days. A torque-angle (T-&) relationship was obtained for 21 joint angles pre- and post-EEX and after four consecutive days of MLL or no-MLL. Muscle wet weights and immunohistochemical sections were obtained after final treatments. Results: EEX produced an average 51% ± 13% decrease in peak isometric torque output. The greatest peak torque recovery occurred with the immediate application of MLL. There were differences in torque recovery between immediate and delayed MLL (P = 0.0012), immediate MLL and control (P < 0.0001), and delayed MLL and control (P = 0.025). Immunohistochemical analysis showed 39.3% and 366.0% differences in the number of RPN3/57 and CD1 lb-positive cells between immediate (P = 0.71) and delayed MLL (P = 0.12). The area under the T-@ curve showed a difference for immediate (P < 0.0001 ) and delayed {P = 0.0051 ) MLL as compared with control. Exercise produced an average 10° ± 0.2° rightward shift from preexercise peak isometric torque angle. Control, immediate MLL, and delayed MLL produced an average leftward angular shift from the postexercise angle (P = 0.28, P = 0.03, and P = 0.47, respectively). Conclusion: Post-EEX, immediate MLL was more beneficial than delayed MLL in restoring muscle function and in modulating inflammatory cell infiltration. These findings invite similar human studies to make definitive conclusions on optimal timing of massage- based therapies. [ABSTRACT FROM AUTHOR]